Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.
ACS Chem Neurosci. 2023 Aug 16;14(16):2827-2829. doi: 10.1021/acschemneuro.3c00482. Epub 2023 Aug 2.
Recent studies involving four research teams have revealed that amyloid fibrils in FTLD-TDP patients and cognitively healthy individuals primarily consist of TMEM106B, a protein previously identified as a risk factor for FTLD-TDP. Through cryogenic electron microscopy, the studies identified various protofilament structures of TMEM106B fibrils from individuals with several neurodegenerative diseases. These findings raise new questions and opportunities for future research, as they suggest that TMEM106B plays a central role in FTLD pathology. These discoveries also prompt the need for the development of specific antibodies for fibrillar TMEM106B and necessitate further investigation of the potential mechanistic link between TMEM106B and other filamentous aggregates. The power of cryo-EM techniques is underscored in these unexpected findings and may be a vital tool for gaining further molecular insights into neurodegenerative diseases characterized by amyloid deposits.
最近涉及四个研究团队的研究表明,FTLD-TDP 患者和认知正常个体中的淀粉样纤维主要由 TMEM106B 组成,TMEM106B 是先前被确定为 FTLD-TDP 风险因素的一种蛋白质。通过低温电子显微镜,这些研究从患有几种神经退行性疾病的个体中鉴定了 TMEM106B 纤维的各种原纤维结构。这些发现为未来的研究提出了新的问题和机会,因为它们表明 TMEM106B 在 FTLD 病理学中发挥核心作用。这些发现还促使人们需要开发针对纤维状 TMEM106B 的特异性抗体,并需要进一步研究 TMEM106B 与其他丝状聚集物之间的潜在机制联系。在这些意外发现中,低温电子显微镜技术的力量得到了强调,它可能是获得对以淀粉样沉积为特征的神经退行性疾病的进一步分子见解的重要工具。